Variant 11-47783196-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015231.3(NUP160):c.3891G>C(p.Lys1297Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NUP160
NM_015231.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

NUP160 (HGNC:18017): (nucleoporin 160) A structural constituent of nuclear pore. Involved in mRNA export from nucleus and nephron development. Part of nuclear pore outer ring. Colocalizes with kinetochore. Implicated in nephrotic syndrome type 19. [provided by Alliance of Genome Resources, Apr 2022]

NUP160 links:

NUP160 (HGNC:):

NUP160 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11372417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP160	NM_015231.3 linkuse as main transcript	c.3891G>C	p.Lys1297Asn	missense_variant, splice_region_variant	34/36	ENST00000378460.7	NP_056046.2	Q12769
NUP160	NR_134636.3 linkuse as main transcript	n.3938G>C		splice_region_variant, non_coding_transcript_exon_variant	34/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NUP160	ENST00000378460.7 linkuse as main transcript	c.3891G>C	p.Lys1297Asn	missense_variant, splice_region_variant	34/36	1	NM_015231.3	ENSP00000367721.3	A0A8V8NBT1
NUP160	ENST00000694866.1 linkuse as main transcript	c.3993G>C	p.Lys1331Asn	missense_variant, splice_region_variant	34/36			ENSP00000511549.1	Q12769-1
NUP160	ENST00000530326.5 linkuse as main transcript	c.3882+1726G>C		intron_variant		5		ENSP00000433590.2	G3V198

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 19

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center

Jun 26, 2024

This sequence variant is a single nucleotide substitution (G>C) at position 3891 of the coding sequence of the NUP160 gene that results in a lysine to asparagine amino acid change at residue 1297 of the nucleoporin 160 protein. This variant is absent from ClinVar and has not been observed in individuals affected by a NUP160-related disorder in the published literature, to our knowledge. This variant is present in 1 of 1613046 alleles (0.00006%) in the gnomAD v4.1.0 population dataset. Bioinformatic tools are inconclusive if this amino acid change will be damaging or tolerated, and the Lys1297 residue at this position is moderately conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.9

DANN

Benign

0.96

DEOGEN2

Benign

0.025

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.23

M_CAP

Benign

0.019

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.1

REVEL

Benign

0.026

Sift

Uncertain

0.016

Sift4G

Benign

0.24

Polyphen

0.51

Vest4

0.35

MutPred

0.36

Loss of solvent accessibility (P = 0.0079);

MVP

0.048

MPC

0.27

ClinPred

0.33

GERP RS

-3.2

Varity_R

0.13

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over